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Effects of the Calcium Channel Blocker Otilonium Bromide on Seizure Activity in Rats With Pentylenetetrazole-Induced Convulsions

Neurochem Res. 2021 Apr 3. doi: 10.1007/s11064-021-03310-4. Online ahead of print.

ABSTRACT

Millions of people suffer from drug-resistant epilepsy. New therapeutic approaches for removing this life-affecting disease are required. The activation of T-type calcium channels (TTCC) is one of the epileptogenesis mechanisms that cause epilepsy. So, we researched the effects of Otilonium bromide (OB), an antisposmolytic drug that inhibits TTCC, on seizure activity in rats with pentylenetetrazol (PTZ) induced convulsion. Randomly, 48 rats were divided into two groups; for electroencephalography (EEG) recordings and for behavioral assesment. Rats were treated with either intraperitoneal (IP) OB at two separate doses (25 mg/kg and 50 mg/kg) or placebo, and then pentylenetetrazole (IP), a potent seizure-inducing chemical administered to them. In our model we have measured rat seizure activity with EEG, the convulsion scala of Racine (RCS), the time of first myoclonic jerk (FMJ) and MDA levels to assess if OB has antiepileptic properties. The mean EEG spike wave percentage score reduced from 79.5% (placebo) to 59.2% (lower-dose) and 35.2% (higher-dose). FMJ had increased from a mean of 67.2 s (placebo), to 105.2 (lower-dose), 150.6 (higher-dose). RCS reduced from a mean of 5.12 (placebo) to 4.4 (lower-dose), 3.8 (higher-dose). MDA leves reduced from 84.5 nmol/gr to 51.09 nmol/gr (lower-dose), 33.2 nmol/gr (higher-dose). Compared to placebo, OB reduced significantly seizure activity at both doses, probably through blocking T-type calcium channels. All these results were statistically significant with < 0.0001 p-values. Otilonium bromide reduced seizure activity in rats with PTZ-induced convulsion. Therefore, the clinical role of OB and other TTCC inhibitors as potential anti-seizure drugs should be further investigated.

PMID:33811624 | DOI:10.1007/s11064-021-03310-4

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Impact of Neoadjuvant Chemotherapy and Pretreatment Biliary Drainage for Pancreatic Head Ductal Adenocarcinoma

Dig Dis Sci. 2021 Apr 3. doi: 10.1007/s10620-021-06967-7. Online ahead of print.

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related deaths in the USA. Although management strategies have evolved, there are continued controversies about the use of neoadjuvant chemotherapy (NAC) and pretreatment biliary drainage (PBD) in patients with resectable and potentially resectable disease.

AIMS: We aimed to characterize the practice trends and outcomes for NAC and PBD.

METHODS: A single-center cohort study was performed. Electronic medical records were reviewed between 2011 and 2019, and 140 patients who had pancreaticoduodenectomy for PDAC were included. Diagnosis, treatment, and outcome data were captured.

RESULTS: There were no statistically significant temporal trends relating to the use of chemotherapy and PBD. Overall, 41% of patients received NAC and had improved survival, independent of other factors. Of the 71% who received PBD, only 40% had appropriate indications; 30% experienced postprocedure complications, and 34% required reintervention. Factors associated with the application of PBD included preoperative jaundice (OR 70.5, 95% CI 21.4-306.6) and evaluation by non-tertiary therapeutic endoscopists (OR 3.9, 95% CI 1.3-13.6). PBD was associated with a 12-day delay in surgery among those who did not receive NAC (p = 0.005), but there were no differences in surgical complications or mortality.

CONCLUSIONS: Our findings suggest that (1) NAC may confer a survival benefit and (2) PBD should be reserved for individuals with jaundice requiring NAC. Implementation of guidelines by North American gastroenterology societies, multidisciplinary treatment models, and delivery of care at high-volume tertiary centers may help optimize management.

PMID:33811566 | DOI:10.1007/s10620-021-06967-7

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Minimally invasive versus conventional continuous-flow left ventricular assist device implantation for heart failure: a meta-analysis

Heart Fail Rev. 2021 Apr 3. doi: 10.1007/s10741-021-10102-z. Online ahead of print.

ABSTRACT

Many studies have reported various minimally invasive techniques for continuous-flow left ventricular assist device implantation. There is no consensus on whether minimally invasive techniques can bring more benefits for patients compared with the conventional technique, due to the limited number of patients and diverse results in current studies. Our meta-analysis mainly discussed the comparison of minimally invasive and conventional techniques. We searched controlled trials from PubMed, Cochrane Library, and Embase databases until Dec 11, 2020. Perioperative and postoperative outcomes were analyzed among 10 included studies. The protocol has been registered with PROSPERO (CRD42020221532). There were no statistical differences in the 30-day mortality (OR 0.57; 95% CI 0.29 to 1.14), 6-month mortality (OR 0.66; 95% CI 0.41 to 1.05), neurological dysfunction (OR 1.10; 95% CI 0.69 to 1.76), major infection (OR 0.68; 95% CI 0.36 to 1.28), and pump thrombus (OR 1.49; 95% CI 0.63 to 3.52) among the cohorts. Minimally invasive techniques were associated with lower incidences of major bleeding (OR 0.39; 95% CI 0.22 to 0.68), severe right heart failure (OR 0.43; 95% CI 0.23 to 0.81), and less blood-product utilization (SMD -0.44). Sensitivity analysis suggested that minimally invasive techniques were associated with a lower incidence of respiratory failure (OR 0.50; 95% CI 0.26 to 0.96) and shorter mechanical ventilation time (SMD -0.53). Subgroup analysis demonstrated that patients, implanted with a centrifugal pump by minimally invasive techniques, were associated with a shorter length of intensive care unit (ICU) stay (SMD -0.27) and hospital stay (SMD -0.42), and less blood-product utilization (SMD -0.26). In conclusion, minimally invasive techniques can reduce the risks of major bleeding, severe right heart failure, and blood-product utilization, as well as have positive impacts on reducing mechanical ventilation time and the risk of respiratory failure. Minimally invasive centrifugal pump implantation can reduce the length of ICU and hospital stay.

PMID:33811570 | DOI:10.1007/s10741-021-10102-z

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Meta-analysis of nanoparticle albumin-bound paclitaxel used as neoadjuvant chemotherapy for operable breast cancer based on individual patient data (JBCRG-S01 study)

Breast Cancer. 2021 Apr 3. doi: 10.1007/s12282-021-01238-9. Online ahead of print.

ABSTRACT

BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-PTX), a novel taxane formulation, was developed to avoid cremophor/ethanol-associated toxicities including peripheral neuropathy and hypersensitivity. At least 35 phase II studies using combined nab-PTX and anthracycline in neoadjuvant settings are registered in Japan. We analyzed the efficacy and safety of nab-PTX based on patient characteristics in these studies.

METHODS: We conducted a meta-analysis using individual patient data (IPD) to investigate the average efficacy of nab-PTX-containing regimens as neoadjuvant chemotherapy for operable breast cancer. IPD were provided by principal investigators who agreed to participate. The primary endpoint was pathological complete response (pCR) rate of each breast cancer subtype.

RESULTS: We analyzed the data of 16 studies involving 753 patients. The overall crude frequencies of pCR (ypT0 ypN0, ypT0/is ypN0, and ypT0/is ypNX) were 18.1, 26.0, and 28.6%, respectively. Specifically, the frequencies were 6.7, 10.2, and 13.4% for luminal (n = 343); 40.5, 63.5, and 68.9% for human epidermal growth factor receptor 2 (HER2)-rich, (n = 74); 21.9, 40.6, and 42.7% for luminal/HER2 (n = 96); and 26.3, 31.5, and 32.3% for triple-negative breast cancers (TNBC) (n = 232). The multivariate analyses indicated that HER2 positivity, TNBC, high Ki-67, high nuclear grade, and weekly nab-PTX administration were significantly associated with the pCR. The proportion of hematological toxicities (neutropenia (39.7%) and leukopenia (22.5%)), peripheral sensory neuropathy (9.7%), myalgia (5.7%), and arthralgia (4.7%) was higher than grade 3 adverse events, but most patients recovered.

CONCLUSIONS: Nab-PTX is a safe and acceptable chemotherapeutic agent in neoadjuvant settings, particularly for aggressive cancers. UMIN-CTR#: UMIN000028774.

PMID:33811599 | DOI:10.1007/s12282-021-01238-9

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Critical speed estimated by statistically appropriate fitting procedures

Eur J Appl Physiol. 2021 Apr 3. doi: 10.1007/s00421-021-04675-8. Online ahead of print.

ABSTRACT

PURPOSE: Intensity domains are recommended when prescribing exercise. The distinction between heavy and severe domains is made by the critical speed (CS), therefore requiring a mathematically accurate estimation of CS. The different model variants (distance versus time, running speed versus time, time versus running speed, and distance versus running speed) are mathematically equivalent. Nevertheless, error minimization along the correct axis is important to estimate CS and the distance that can be run above CS (d’). We hypothesized that comparing statistically appropriate fitting procedures, which minimize the error along the axis corresponding to the properly identified dependent variable, should provide similar estimations of CS and d’ but that different estimations should be obtained when comparing statistically appropriate and inappropriate fitting procedure.

METHODS: Sixteen male runners performed a maximal incremental aerobic test and four exhaustive runs at 90, 100, 110, and 120% of their peak speed on a treadmill. Several fitting procedures (a combination of a two-parameter model variant and regression analysis: weighted least square) were used to estimate CS and d’.

RESULTS: Systematic biases (P < 0.001) were observed between each pair of fitting procedures for CS and d’, even when comparing two statistically appropriate fitting procedures, though negligible, thus corroborating the hypothesis.

CONCLUSION: The differences suggest that a statistically appropriate fitting procedure should be chosen beforehand by the researcher. This is also important for coaches that need to prescribe training sessions to their athletes based on exercise intensity, and their choice should be maintained over the running seasons.

PMID:33811559 | DOI:10.1007/s00421-021-04675-8

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Observation of therapeutic effect on coronavirus disease 2019 with insomnia in treatment with baduanjin and auricular point sticking therapy

Zhongguo Zhen Jiu. 2021 Mar 12;41(3):243-6. doi: 10.13703/j.0255-2930.20200327-0002.

ABSTRACT

OBJECTIVE: To compare the clinical therapeutic effect on coronavirus disease 2019 (COVID-19) with insomnia between the combined treatment of baduanjin and auricular point sticking therapy and the medication with oral estazolam on the base of the conventional treatment.

METHODS: A total of 90 patients with COVID-19 accompanied with insomnia were randomly divided into an observation group (45 cases, 3 cases dropped off) and a control group (45 cases). In the observation group, baduanjin, a traditional Chinese fitness activity, was practiced everyday. Besides, auricular point sticking therapy was exerted at ear-shenmen (TF 4), subcortex (AT 4), heart (CO 15), occiput (AT 3), etc. These auricular points were pressed and kneaded three times a day, 30 s at each point each time, consecutively for 12 days. In the control group, estazolam tablets were prescribed for oral administration, 1 mg, once daily, consecutively for 12 days. Before and after treatment, the score of Pittsburgh sleep quality index (PSQI), the score of self-rating anxiety scale (SAS), the score of self-rating depression scale (SDS) and the score of symptoms in traditional Chinese medicine (TCM) were observed in the two groups and the clinical therapeutic effect was evaluated.

RESULTS: After treatment, the scores of every item and the total scores in PSQI were all reduced as compared with those before treatment in the two groups (P<0.01). The scores of sleep time and sleep efficiency in the observation group were lower than those in the control group after treatment (P<0.05). SAS scores and SDS scores in the observation group and SAS score in the control group after treatment were all reduced as compared with those before treatment (P<0.01), and SDS score in the observation group was lower than that in the control group (P<0.01). After treatment, in the observation group, the score of each of the symptoms of TCM, i.e. unsound sleep, irritability and hot temper, profuse sputum and sticky feeling in the mouth, bitter taste in the mouth and foul breath, abdominal distention and poor appetite, as well as lassitude was reduced as compared with that before treatment successively (P<0.01), and the scores aforementioned (excepted for the unsound sleep) in the observation group were all lower than the control group (P<0.05). The total effective rates were 83.3% (35/42) in the observation group and 84.4% (38/45) in the control group, without statistical difference in comparison (P>0.05).

CONCLUSION: The combined treatment of baduanjin and auricular point sticking therapy improves sleep quality, the conditions of anxiety and depression and the symptoms in TCM for patients of COVID-19 with insomnia. The therapeutic effect of this combined treatment is better than the oral administration of estazolam.

PMID:33798303 | DOI:10.13703/j.0255-2930.20200327-0002

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Influence of electroacupuncture on the expression of AMPA receptor subunit GluR1 in the spinal injured area of the rats with acute spinal cord injury

Zhongguo Zhen Jiu. 2021 Mar 12;41(3):307-12. doi: 10.13703/j.0255-2930.20200317-k0005.

ABSTRACT

OBJECTIVE: To explore the influence of electroacupuncture (EA) on the expression of AMPA receptor subunit GluR1 in the rats with acute spinal cord injury (SCI) and explore the potential effect mechanism of EA in treatment of acute SCI.

METHODS: A total of 80 SD rats were randomly divided into five groups, i.e. a sham-operation group, a model group, an AMPA antagonist (DNQX) group, an EA group and a DNQX+EA group, 16 rats in each group. The modified Allen’s impacting method was adopted to prepare the rat model of acute SCI at T10. In the DNQX group, the intrathecal injection of 10 μL DNQX solution with a concentration of 1 nmol/μL was administered in 0.5 h after modeling success. In the EA group, EA (disperse-dense wave, 2 Hz/100 Hz in frequency, 0.5 mA in output current) was given at “Dazhui” (GV 14) and “Mingmen” (GV 4) in 0.5 h, 12 h and 24 h after modeling success for 30 min and totally 3 times. In the DNQX + EA group, the interventions in the above two groups were managed. The Basso, Beattie and Bresnahan locomotor rating score (BBB) was applied to evaluate the changes of locomotor function in the rats before modeling and in 6 h, 24 h and 48 h after modeling successively. Using the hematoxylin-eosin (HE) staining, the histopathological changes in the spinal anterior horn were observed in the spinal injured area. The immunofluorescence method was adopted to determine the number of GluR1 positive neuron of the spinal anterior horn. The Western blot method was used to determine the protein expression of GluR1 in the injured area.

RESULTS: Compared to the sham-operation group in 6 h, 24 h and 48 h after modeling, the BBB scores were all significantly decreased in the model group (P<0.001) at the corresponding points. The BBB score was increased in each of intervention groups, but without statistical difference as compared with the model group (P>0.05). In the model group, it was found that the boundary between gray matter and white matter in the spinal anterior horn was blurred, the interstitial space enlarged, the neuron volume obviously shrunken, the cytoplasm decreased, the red stain deepened and some neuron nuclei fixed and shrunk. In the EA group, the morphology of the spinal anterior horn in the injured area was improved obviously, which was similar in the DNQX group and the DNQX + EA group. Compared with the sham-operation group, the GluR1 protein expression in the spinal injury area was increased (P<0.001) and the number of GluR1 positive neurons elevated (P<0.001) in the spinal anterior horn in the model group. Compared with the model group, in the EA group, the DNQX group and the DNQX + EA group, GluR1 protein expression was decreased (P<0.05, P<0.01) and the number of GluR1 positive neurons in the spinal anterior horn reduced (P<0.001).

CONCLUSION: The intervention with EA at “Dazhui” and “Mingmen” promotes the repair of the injured nerve in the spinal anterior horn probably through inhibiting GluR1 expression in the spinal injured area in the rats with acute SCI.

PMID:33798315 | DOI:10.13703/j.0255-2930.20200317-k0005

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Region identification of Xinyang Maojian tea using UHPLC-Q-TOF/MS-based metabolomics coupled with multivariate statistical analyses

J Food Sci. 2021 Apr 2. doi: 10.1111/1750-3841.15676. Online ahead of print.

ABSTRACT

Xinyang Maojian tea is a kind of famous roasted green tea produced in the middle of China. Ultra-high performance liquid chromatography-quadrupole time of flight-mass spectrometry (UHPLC-Q-TOF/MS)-based metabolomics coupled with multivariate statistical analyses, including principal component analysis (PCA) and hierarchical cluster analysis (HCA), were carried out in XMMJTs collected from Luoshan, Shangcheng, and Shihe Counties, respectively. Additionally, seven catechins, four flavonoids, two purine alkaloids, and gallic acid contents were determined by HPLC. Differential metabolites were selected by p-value <0.05, and fold change >1.50 or < 0.66 among 745 detected metabolites in metabolomics analysis. The results showed significant (p < 0.05) differences of three catechins including (-)-epicatechin, (-)-epicatechin gallate, and (-)-gallocatechin gallate, four flavonoids (i.e. quercetin, kaempferol, myricetin, and rutin), and theobromine among three various regions, and significant (p < 0.05) differences of (-)-epicatechin gallate, (-)-epigallocatechin, (+)-catechin, gallic acid, and kaempferol between Shuchazao and Group cultivar. The HCA showed that, except for two samples (i.e. LS 2 and SH 2) of Shuchazao cultivar clustered together, others could be clustered completely according to production place. The 63 relevant differential metabolites could achieve the purpose of region identification through PCA. Kyoto encyclopedia of genes and genomes (KEGG) metabolic pathway analysis elaborated the impact of geographical origin and tea cultivar on physiological metabolism in tea tree. PRACTICAL APPLICATION: Ultra-high performance liquid chromatography-quadrupole time of flight-mass spectrometry (UHPLC-Q-TOF/MS)-based liquid chromatography-tendem mass spectrometry (LC-MS/MS) metabolomics coupled with multivariate statistical analyses, such as principal component analysis (PCA) and hierarchical cluster analysis (HCA), revealed 63 differential metabolites related to production place, which contributed to the region identification of Xinyang Maojian teas.

PMID:33798265 | DOI:10.1111/1750-3841.15676

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Effect of transcutaneous electrical acupoint stimulation combined with epidural labor analgesia on postpartum depression

Zhen Ci Yan Jiu. 2021 Mar 25;46(3):231-4. doi: 10.13702/j.1000-0607.200249.

ABSTRACT

OBJECTIVE: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS)combined with epidural analgesia on postpartum depression and to explore its underlying mechanism.

METHODS: One hundred and twenty cases of full-term primiparous women with singleton pregnancy were selected from May 2018 to November 2018 in Jinzhong Maternal and Child Health Hospital. The parturients with labor analgesia requirement were randomly divided into the epidural group and the combination group, and the parturients without labor analgesia requirement were used as the control group, with 40 cases in each group. Patients in the control group did not receive labor analgesia and were treated according to the routine procedures of natural delivery; patients in the epidural group received epidural labor analgesia; patients in the combination group received TEAS at bilateral Hegu(LI4), Sanyinjiao(SP6) and Zusanli(ST36) (2 Hz/100 Hz, the current intensity is gradually increased from 15 mA, and the treatment was performed every 2 h, 20 min each time) combined with epidural labor analgesia. The visual analogue scale (VAS) scores were recorded when the uterine orifice opened to 3, 6, 8, 10 cm. Plasma glutamate was measured using high-performance liquid chromatography before analgesia, at the end of the third stage of labor and 42 days after delivery, and Edinburgh postnatal depression scale (EPDS) score was measured at 42 days after delivery.

RESULTS: In comparison with the control group, the VAS score, EPDS score and the incidence of postpartum depression of the epidural group and the combination group were significantly lower(P<0.05), and the combination group had significant decrease than those in epidural group (P<0.05). Immediately before analgesia, there was no statistically significant difference in glutamate levels among the 3 groups (P>0.05). Compared with the control group, at the end of the third stage of labor and 42 days postpartum, the glutamate levels of the epidural group and the combination group were significantly reduced(P<0.05), and the combination group decreased more significantly than the epidural group (P<0.05).

CONCLUSION: TEAS combined with epidural analgesia can reduce the incidence of postpartum depression, possibly by down-regulating plasma glutamate level and relieving of labor pain.

PMID:33798297 | DOI:10.13702/j.1000-0607.200249

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Characteristics of clinical application of electroacupuncture therapy for peripheral neuropathy based on data mining

Zhen Ci Yan Jiu. 2021 Mar 25;46(3):240-7. doi: 10.13702/j.1000-0607.200638.

ABSTRACT

OBJECTIVE: To investigate the application characteristics of electroacupuncture (EA) in the treatment of peripheral neuropathy, so as to provide a basis for clinical use of EA therapy.

METHODS: Keywords of “electroacupuncture””peripheral neuropathy” “facial paralysis” “trigeminal neuralgia” “sciatica” “common peroneal nerve injury” “diabetic peripheral neuropathy” “intercostal neuralgia” “gluteal epithelial neuritis” “ulnar nerve injury” “median nerve paralysis” “postherpetic neuralgia”, and “great occipital neuralgia” were used to search articles in both English and Chinese published from 1999 to 2019 in databases of CNKI, Wanfang, VIP, CBM, Ovid, PubMed and Embase and related books such as electroacupuncture, and neurology, followed by establishing a database of “Electroacupuncture Treatment of Peripheral Neuropathy”. Then, the collected articles were put into statistical analysis after sorting, screening, input, checking, and data extracting by using data mining technology and statistical software EpiData.

RESULTS: Of the searched 1 528 papers, 778 were eligible, involving 13 types of peripheral neuropathy which the facial paralysis and facial spasm were most frequently seen, followed by trigeminal neuralgia and sciatica, with an effective rate being above 90% for nearly all the 13 diseases. The acupoints employed were chiefly those close to the affected area and distribute along the nerve trunk.In addition, about the needling techniques, the penetration needling was frequently used, and the triple needling, quintuple needling and accompanied needling were also used. Regarding the related needle manipulations, the uniform reinforcing-reduction technique was most frequently used. The duration of EA was 30 min, with a highest stimulating frequency of 50 Hz. The acupoint injection was frequently supplemented, followed by moxibustion, and the treatment sessions were usually about 30 times.

CONCLUSION: EA therapy is frequently used in the treatment of peripheral neuropathy, and has some characteristics in acupoint selection, stimulating parameters and some additional needling techniques.

PMID:33798299 | DOI:10.13702/j.1000-0607.200638